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1.
Small ; 19(45): e2303783, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37434076

ABSTRACT

Hydrogels, as well as colloidal hydrogels (microgels), are important materials for a large variety of applications in the biomedical field. Microgels with a controlled pore size (meso- and macropores) are required for efficient nutrient support, modulation of cell adhesion, removal of metabolic products in cell cultures, and probiotic loading. Common microgel fabrication techniques do not provide sufficient control over pore sizes and geometry. In this work, the natural polysaccharide dextran modified with methacrylate groups is used to synthesize highly monodisperse meso- and macroporous microgels in a size range of 100-150 µm via photo cross-linking in microfluidic droplets. The size of mesopores is varied by the concentration of dextran methacrylate chains in the droplets (50-200 g L-1 ) and the size of macropores is regulated by the integration of pH-degradable supramacromolecular nanogels with diameters of 300 and 700 nm as sacrificial templates. Using permeability assays combined with confocal laser scanning microscopy, it is demonstrated that functional dextran-based microgels with uniform and defined pores could be obtained.

2.
Chem Sci ; 13(38): 11304-11311, 2022 Oct 05.
Article in English | MEDLINE | ID: mdl-36320583

ABSTRACT

In the context of controlled delivery and release, proteins constitute a delicate class of cargo requiring advanced delivery platforms and protection. We here show that mechanoresponsive diselenide-crosslinked microgels undergo controlled ultrasound-triggered degradation in aqueous solution for the release of proteins. Simultaneously, the proteins are protected from chemical and conformational damage by the microgels, which disintegrate to water-soluble polymer chains upon sonication. The degradation process is controlled by the amount of diselenide crosslinks, the temperature, and the sonication amplitude. We demonstrate that the ultrasound-mediated cleavage of diselenide bonds in these microgels facilitates the release and activates latent functionality preventing the oxidation and denaturation of the encapsulated proteins (cytochrome C and myoglobin) opening new application possibilities in the targeted delivery of biomacromolecules.

3.
Chem Soc Rev ; 51(8): 2939-2956, 2022 Apr 19.
Article in English | MEDLINE | ID: mdl-35319064

ABSTRACT

Microgels are colloidal polymer networks with high molar mass and properties between rigid particles, flexible macromolecules, and micellar aggregates. Their unique stimuli-responsiveness in conjunction with their colloidal phase behavior render them useful for many applications ranging from engineering to biomedicine. In many scenarios either the microgel's mechanical properties or its interactions with mechanical force play an important role. Here, we firstly explain microgel mechanical properties and how these are measured by atomic force microscopy (AFM), then we equip the reader with the synthetic background to understand how specific architectures and chemical functionalities enable these mechanical properties, and eventually we elucidate how the interaction of force with microgels can lead to the activation of latent functionality. Since the interaction of microgels with force is a multiscale and multidisciplinary subject, we introduce and interconnect the different research areas that contribute to the understanding of this emerging field in this Tutorial Review.


Subject(s)
Microgels , Microscopy, Atomic Force , Molecular Weight , Polymers/chemistry
4.
Sci Rep ; 12(1): 4508, 2022 03 16.
Article in English | MEDLINE | ID: mdl-35296685

ABSTRACT

Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Histopathological confirmation is a key step in tumor diagnosis. Therefore, simplification in decision-making by discrimination between malignant and non-malignant cells of histological specimens can be provided by combination of new imaging technology and artificial intelligence (AI). In this work, hyperspectral imaging (HSI) data from 95 patients were used to classify three different histopathological features (squamous epithelium cells, esophageal adenocarcinoma (EAC) cells, and tumor stroma cells), based on a multi-layer perceptron with two hidden layers. We achieved an accuracy of 78% for EAC and stroma cells, and 80% for squamous epithelium. HSI combined with machine learning algorithms is a promising and innovative technique, which allows image acquisition beyond Red-Green-Blue (RGB) images. Further method validation and standardization will be necessary, before automated tumor cell identification algorithms can be used in daily clinical practice.


Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Esophageal Neoplasms , Adenocarcinoma/diagnostic imaging , Artificial Intelligence , Esophageal Neoplasms/diagnostic imaging , Humans , Hyperspectral Imaging
5.
Adv Sci (Weinh) ; 9(12): e2104004, 2022 04.
Article in English | MEDLINE | ID: mdl-35187862

ABSTRACT

Microgels (µgels) swiftly undergo structural and functional degradation when they are exposed to shear forces, which potentially limit their applicability in, e.g., biomedicine and engineering. Here, poly(N-vinylcaprolactam) µgels that resist mechanical disruption through supramolecular hydrogen bonds provided by (+)-catechin hydrate (+C) are synthesized. When +C is added to the microgel structure, an increased resistance against shear force exerted by ultrasonication is observed compared to µgels crosslinked by covalent bonds. While covalently crosslinked µgels degrade already after a few seconds, it is found that µgels having both supramolecular interchain interactions and covalent crosslinks show the highest mechanical durability. By the incorporation of optical force probes, it is found that the covalent bonds of the µgels are not stressed beyond their scission threshold and mechanical energy is dissipated by the force-induced reversible dissociation of the sacrificial +C bonds for at least 20 min of ultrasonication. Additionally, +C renders the µgels pH-sensitive and introduces multiresponsivity. The µgels are extensively characterized using Fourier-transform infrared, Raman and quantitative nuclear magnetic resonance spectroscopy, dynamic light scattering, and cryogenic transmission electron microscopy. These results may serve as blueprint for the preparation of many mechanically durable µgels.


Subject(s)
Catechin , Microgels , Caprolactam/analogs & derivatives , Hydrogen Bonding , Polymers/chemistry
6.
J Gastrointest Cancer ; 53(4): 948-957, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34559362

ABSTRACT

PURPOSE: Early detection of adenocarcinomas in the esophagus is crucial for achieving curative endoscopic therapy. Targeted biopsies of suspicious lesions, as well as four-quadrant biopsies, represent the current diagnostic standard. However, this procedure is time-consuming, cost-intensive, and examiner-dependent. The aim of this study was to test whether impedance spectroscopy is capable of distinguishing between healthy, premalignant, and malignant lesions. An ex vivo measurement method was developed to examine esophageal lesions using impedance spectroscopy immediately after endoscopic resection. METHODS: After endoscopic resection of suspicious lesions in the esophagus, impedance measurements were performed on resected cork-covered tissue using a measuring head that was developed, with eight gold electrodes, over 10 different measurement settings and with frequencies from 100 Hz to 1 MHz. RESULTS: A total of 105 measurements were performed in 60 patients. A dataset of 400 per investigation and a total of more than 42,000 impedance measurements were therefore collected. Electrical impedance spectroscopy (EIS) was able to detect dysplastic esophageal mucosa with a sensitivity of 81% in Barrett's esophagus. CONCLUSION: In summary, EIS was able to distinguish different tissue characteristics in the different esophageal tissues. EIS thus holds potential for further development of targeted biopsies during surveillance endoscopy. Trial Registration NCT04046601.


Subject(s)
Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Humans , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Barrett Esophagus/diagnosis , Barrett Esophagus/surgery , Barrett Esophagus/pathology , Biopsy/methods , Dielectric Spectroscopy , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Esophagoscopy/methods
7.
Procedia Comput Sci ; 175: 56-63, 2020.
Article in English | MEDLINE | ID: mdl-32834877

ABSTRACT

New work models have been discussed for several years. Especially in the area of knowledge work, mobile and distributed work provides advantages over presence time at companies: It offers more freedom and flexibility to the employees, reduces travel time, and counteracts a major trend: the exodus from rural areas. However, to provide an optimized digital work environment for distributed teams of knowledge workers, many different aspects must be considered, including social, physical, legal, and technological aspects. In this article, we focus on the technological aspects. Nowadays, a multitude of tools and technologies exist to support the communication of distributed teams, to allow working concurrently on documents, or to support data and document exchange. However, many existing solutions only provide solutions for a specific purpose rather than a sophisticated platform that offers all of these services in an integrated manner and additionally takes care of delivering intelligent and data-driven services in a trustful and ethical way. In the research project "Digital Teams", we aim at developing such a platform as open source. In this article, we provide the basic architecture of our platform and share the main concepts and solutions we are currently implementing, such as our dashboard, data exchange concepts, or authentication and authorization mechanisms.

8.
Biomacromolecules ; 21(2): 974-987, 2020 02 10.
Article in English | MEDLINE | ID: mdl-31940180

ABSTRACT

Glycosidases have long been used for the synthesis of glycosides by transglycosylation reactions. Especially glycosidases from hyperthermophilic bacteria are useful for reactions under extreme reaction conditions, e.g., in the presence of organic solvents. We herein report the facile enzymatic synthesis and purification of 2-(ß-galactosyl)-ethyl methacrylate (Gal-EMA) with the recombinant hyperthermostable glycosidase from Pyrococcus woesei in high yields. Optimized reaction conditions resulted in gram-scale synthesis of the galactosylated monomer with 88% transglycosylation yield. The product Gal-EMA was characterized by high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) spectroscopy. Gal-EMA was utilized to synthesize sugar-functionalized acrylate polymers with defined amounts of incorporated galactose (0-100%). Analysis of the binding affinity of the lectin RCA120 from Ricinus communis to the glycopolymers using an enzyme-linked lectin assay (ELLA) revealed KD values between 0.24 and 6.2 nM, depending on the amount of incorporated Gal-EMA. The potential of Gal-EMA for the synthesis of acrylate-functionalized glycan oligomers was demonstrated by sequential elongation of the terminal galactose by two glycosyltransferases, resulting in the terminal glycan N-acetyllactosamine (LacNAc) epitope. In conclusion, the enzymatic synthesis of Gal-EMA opens new routes to a series of novel monomeric building blocks for the synthesis of glycan-functionalized polyacrylates.


Subject(s)
Lectins/metabolism , Methacrylates/metabolism , Polymers/metabolism , Pyrococcus/enzymology , beta-Galactosidase/metabolism , Humans , Lectins/chemical synthesis , Methacrylates/chemical synthesis , Polymers/chemical synthesis , Spectrometry, Mass, Electrospray Ionization/methods , beta-Galactosidase/chemical synthesis
9.
World J Surg ; 44(4): 1192-1199, 2020 04.
Article in English | MEDLINE | ID: mdl-31853591

ABSTRACT

BACKGROUND: Research in early esophageal adenocarcinoma focused on prediction of lymph node metastases in order to stratify patients for endoscopic treatment instead of esophagectomy. Although distant metastases were described in rates of up to 13% of patients within a follow-up of 3 years, their prediction has been neglected so far. METHODS: In a secondary analysis, a cohort of 217 patients (53 T1a and 164 T1b) treated by esophagectomy was analyzed for histopathological risk factors. Their ability to predict the combination of lymph node metastases at surgery as well as metachronous locoregional and distant metastases (overall metastatic rate) was assessed by uni- and multivariate logistic regression analysis. RESULTS: Tumor invasion depth was correlated with both lymph node metastases at surgery (τ = 0.141; P = .012), tumor recurrences (τ = 0.152; P = .014), and distant metastases (τ = 0.122; P = 0.04). Multivariate analysis showed an odds ratio of 1.31 (95% CI 1.02-1.67; P = .033) per increasing tumor invasion depth and of 3.5 (95% CI 1.70-6.56; P < .001) for lymphovascular invasion. The pre-planned subgroup analysis in T1b tumors demonstrated an even lower predictive ability of lymphovascular invasion with an odds ratio of 2.5 (95% CI 1.11-5.65; P = 0.028), whereas the predictive effect of sm2 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) and sm3 (odds ratio 3.44; 95% CI 1.00-11.9; P = 0.049) tumor invasion depth was similar. CONCLUSIONS: The present report demonstrates the insufficient risk prediction of histopathologic risk factors for the overall metastatic rate.


Subject(s)
Adenocarcinoma/pathology , Esophageal Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Aged , Esophageal Neoplasms/surgery , Esophagectomy , Female , Humans , Logistic Models , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Risk Factors
10.
Planta ; 249(5): 1337-1347, 2019 May.
Article in English | MEDLINE | ID: mdl-30631956

ABSTRACT

MAIN CONCLUSION: Chloroplasts deficient in the major chloroplast nucleoid-associated protein WHIRLY1 have an enhanced ratio of LHCs to reaction centers, indicating that WHIRLY1 is required for a coordinate assembly of the photosynthetic apparatus during chloroplast development. Chloroplast development was found to be delayed in barley plants with an RNAi-mediated knockdown of WHIRLY1 encoding a major nucleoid-associated protein of chloroplasts. The plastids of WHIRLY1 deficient plants had a reduced ribosome content. Accordingly, plastid-encoded proteins of the photosynthetic apparatus showed delayed accumulation during chloroplast development coinciding with a delayed increase in photosystem II efficiency measured by chlorophyll fluorescence. In contrast, light harvesting complex proteins being encoded in the nucleus had a high abundance as in the wild type. The unbalanced assembly of the proteins of the photosynthetic apparatus in WHIRLY1-deficient plants coincided with the enhanced contents of chlorophyll b and xanthophylls. The lack of coordination was most obvious at the early stages of development. Overaccumulation of LHC proteins in comparison to reaction center proteins at the early stages of chloroplast development did not correlate with enhanced expression levels of the corresponding genes in the nucleus. This work revealed that WHIRLY1 does not influence LHC abundance at the transcriptional level. Rather, WHIRLY1 in association with nucleoids might play a structural role for both the assembly of ribosomes and the complexes of the photosynthetic apparatus.


Subject(s)
Cell Nucleus/metabolism , Chloroplasts/metabolism , Hordeum/metabolism , Plant Proteins/metabolism , Plastids/metabolism , Chlorophyll/metabolism , Gene Expression Regulation, Plant , Hordeum/genetics , Plant Proteins/genetics
11.
Front Neurol ; 10: 1377, 2019.
Article in English | MEDLINE | ID: mdl-32038458

ABSTRACT

Glucocorticoids are used intra-operatively in cochlear implant surgeries to reduce the inflammatory reaction caused by insertion trauma and the foreign body response against the electrode carrier after cochlear implantation. To prevent higher systemic concentrations of glucocorticoids that might cause undesirable systemic side effects, the drug should be applied locally. Since rapid clearance of glucocorticoids occurs in the inner ear fluid spaces, sustained application is supposedly more effective in suppressing foreign body and tissue reactions and in preserving neuronal structures. Embedding of the glucocorticoid dexamethasone into the cochlear implant electrode carrier and its continuous release may solve this problem. The aim of the present study was to examine how dexamethasone concentrations in the electrode carrier influence drug levels in the perilymph at different time points. Silicone rods were implanted through a cochleostomy into the basal turn of the scala tympani of guinea pigs. The silicone rods were loaded homogeneously with 0.1, 1, and 10% concentrations of dexamethasone. After implantation, dexamethasone concentrations in perilymph and cochlear tissue were measured at several time points over a period of up to 7 weeks. The kinetic was concentration-dependent and showed an initial burst release in the 10%- and the 1%-dexamethasone-loaded electrode carrier dummies. The 10%-loaded electrode carrier resulted in a more elevated and longer lasting burst release than the 1%-loaded carrier. Following this initial burst release phase, sustained dexamethasone levels of about 60 and 100 ng/ml were observed in the perilymph for the 1 and 10% loaded rods, respectively, during the remainder of the observation time. The 0.1% loaded carrier dummy achieved very low perilymph drug levels of about 0.5 ng/ml. The cochlear tissue drug concentration shows a similar dynamic to the perilymph drug concentration, but only reaches about 0.005-0.05% of the perilymph drug concentration. Dexamethasone can be released from silicone electrode carrier dummies in a controlled and sustained way over a period of several weeks, leading to constant drug concentrations in the scala tympani perilymph. No accumulation of dexamethasone was observed in the cochlear tissue. In consideration of experimental studies using similar drug depots and investigating physiological effects, an effective dose range between 50 and 100 ng/ml after burst release is suggested for the CI insertion trauma model.

13.
Food Res Int ; 110: 3-10, 2018 08.
Article in English | MEDLINE | ID: mdl-30029703

ABSTRACT

During the 20th century, the economic position of oats (Avena sativa L.) decreased strongly in favour of higher yielding crops including winter wheat and maize. Presently, oat represents only ~1.3% of the total world grain production, and its production system is fragmented. Nonetheless, current interest is growing because of recent knowledge on its potential benefits in food, feed and agriculture. This perspective will serve as a further impetus, with special focus on the recently valued advantages of oats in human food and health. Five approved European Food Safety Authority (EFSA) health claims apply to oats. Four relate to the oat-specific soluble fibres, the beta-glucans, and concern the maintenance and reduction of blood cholesterol, better blood glucose balance and increased faecal bulk. The fifth claim concerns the high content of unsaturated fatty acids, especially present in the endosperm, which reduces the risks of heart and vascular diseases. Furthermore, oat starch has a low glycemic index, which is favourable for weight control. Oat-specific polyphenols and avenanthramides have antioxidant and anti-inflammatory properties. Thus, oats can contribute significantly to the presently recommended whole-grain diet. Next to globulins, oats contain a small fraction of prolamin storage proteins, called 'avenins', but at a much lower quantity than gluten proteins in wheat, barley and rye. Oat avenins do not contain any of the known coeliac disease epitopes from gluten of wheat, barley and rye. Long-term food studies confirm the safety of oats for coeliac disease patients and the positive health effects of oat products in a gluten-free diet. These effects are general and independent of oat varieties. In the EU (since 2009), the USA (since 2013) and Canada (since 2015) oat products may be sold as gluten-free provided that any gluten contamination level is below 20ppm. Oats are, however, generally not gluten-free when produced in a conventional production chain, because of regular contamination with wheat, barley or rye. Therefore, establishing a separate gluten-free oat production chain requires controlling all steps in the chain; the strict conditions will be discussed. Genomic tools, including a single nucleotide polymorphism (SNP) marker array and a dense genetic map, have recently been developed and will support marker-assisted breeding. In 2015, the Oat Global initiative emerged enabling a world-wide cooperation starting with a data sharing facility on genotypic, metabolic and phenotypic characteristics. Further, the EU project TRAFOON (Traditional Food Networks) facilitated the transfer of knowledge to small- and medium-sized enterprises (SMEs) to stimulate innovations in oat production, processing, products and marketing, among others with regard to gluten-free. Finally, with focus on counteracting market fragmentation of the global oat market and production chains, interactive innovation strategies between customers (consumers) and companies through co-creation are discussed.


Subject(s)
Avena , Diet/methods , Diet, Gluten-Free/methods , Humans
14.
Front Psychol ; 8: 773, 2017.
Article in English | MEDLINE | ID: mdl-28579967

ABSTRACT

Narcissists often pursue leadership and are selected for leadership positions by others. At the same time, they act in their own best interest, putting the needs and interests of others at risk. While theoretical arguments clearly link narcissism and leadership, the question whether leader narcissism is good or bad for organizations and their members remains unanswered. Narcissism seems to have two sides, a bright and a dark one. This systematic literature review seeks to contribute to the ongoing academic discussion about the positive or negative impact of leader narcissism in organizations. Forty-five original research articles were categorized according to outcomes at three levels of analysis: the dyadic level (focusing on leader-follower relationships), the team level (focusing on work teams and small groups), and the organizational level. On this basis, we first summarized the current state of knowledge about the impact that leader narcissism has on outcomes at different levels of analysis. Next, we revealed similarities and contradictions between research findings within and across levels of analysis, highlighting persistent inconsistencies concerning the question whether leader narcissism has positive or negative consequences. Finally, we outlined theoretical and methodological implications for future studies of leader narcissism. This multi-level perspective ascertains a new, systematic view of leader narcissism and its consequences for organizations and their stakeholders. The article demonstrates the need for future research in the field of leader narcissism and opens up new avenues for inquiry.

15.
Eur Arch Otorhinolaryngol ; 273(7): 1745-53, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26319276

ABSTRACT

Cochlear implants have been widely used for patients with profound hearing loss and partial deafness. Residual low-frequency hearing, however, may deteriorate due to insertion trauma and tissue response around the electrode array. The present study investigated in vitro and in vivo release of dexamethasone from silicone used for cochlear implant electrode carriers. The in vitro experiment involved an apparatus simulating the inner ear fluid environment in humans. Release from two sizes of silicone films (200 µm × 1 mm × 10 mm and 500 µm × 1 mm × 10 mm), each loaded with 2 % dexamethasone, and was measured for 24 weeks. In the in vivo experiment, silicone rods loaded with 2 or 10 % dexamethasone, respectively, were implanted into the scala tympani of guinea pigs. Perilymph concentrations were measured during the first week after implantation. The results showed that dexamethasone was released from the silicone in a sustained manner. After a burst release, perilymph concentration was similar for silicone incorporated with 2 and 10 % dexamethasone, respectively. The similar pharmacokinetic profile was found in the in vitro experiment. The period of sustained drug delivery was maintained for 20 weeks in vitro and for 1 week in vivo. The results of the present study suggest that drugs like dexamethasone are released in a controlled manner from silicon electrode carriers of cochlear implants. Further studies will identify optimal release profiles for the use with cochlear implants to improve their safety and long-term performance.


Subject(s)
Cochlear Implants , Dexamethasone/pharmacokinetics , Glucocorticoids/pharmacokinetics , Silicones , Animals , Cochlear Implantation , Dexamethasone/administration & dosage , Drug Delivery Systems , Glucocorticoids/administration & dosage , Guinea Pigs , Hearing Loss/surgery , Humans , Perilymph/metabolism , Scala Tympani/surgery
16.
Hear Res ; 327: 89-101, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25987502

ABSTRACT

AIM: This study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation. METHODS: Guinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann-Whitney U test (1-tailed) was used for statistical analyses. RESULTS: ABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4-24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively. CONCLUSION: Cochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.


Subject(s)
Cochlea/drug effects , Cochlear Implants , Dexamethasone/administration & dosage , Dexamethasone/pharmacokinetics , Glucocorticoids/administration & dosage , Glucocorticoids/pharmacokinetics , Hearing Loss/prevention & control , Hearing/drug effects , Acoustic Stimulation , Animals , Auditory Threshold/drug effects , Chromatography, High Pressure Liquid , Cochlea/metabolism , Cochlea/pathology , Cochlea/physiopathology , Disease Models, Animal , Drug Implants , Evoked Potentials, Auditory, Brain Stem/drug effects , Fibrosis , Guinea Pigs , Hearing Loss/diagnosis , Hearing Loss/etiology , Hearing Loss/metabolism , Hearing Loss/physiopathology , Otoacoustic Emissions, Spontaneous/drug effects , Perilymph/metabolism , Silicones/chemistry , Tumor Necrosis Factor-alpha/metabolism
17.
Acta Otolaryngol ; 132(12): 1252-60, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22992177

ABSTRACT

CONCLUSION: Dexamethasone released from a cochlear implant seems not to enhance the risk for postoperative infections. OBJECTIVE: Dexamethasone has a positive impact on hearing preservation for electric acoustic stimulation (EAS). Due to their antiproliferative and immunosuppressive properties, steroids may enhance the risk of postoperative infections. A comparative study was performed to evaluate the risk of pneumococcal meningitis after implantation of dexamethasone-eluting cochlear implants. METHODS: Thirty guinea pigs were implanted with non-eluting (n = 15) or dexamethasone-eluting (n = 15) cochlear implant electrode dummies. After 5 weeks, animals were exposed to a virulent strain of Streptococcus pneumoniae. The two groups were compared based on the meningitis rate. Animals were observed for 5 days for signs of meningitis. Meningitis was verified by clinical outcome as well as by pleocytosis and presence of bacteria in cerebrospinal fluid. Results were confirmed by histological examination of brains and cochleae, clinical findings and culture. RESULTS: There was no significant difference in meningitis risk between the two groups. In the group with non-eluting implants, 3 of 15 animals developed meningitis, while in the group with dexamethasone-eluting implants 4 of 15 showed signs of meningitis. In this study dexamethasone-releasing implants did not significantly increase the risk of postoperative pneumococcal otogenic meningitis.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Cochlear Implants , Dexamethasone/administration & dosage , Meningitis, Pneumococcal/prevention & control , Prosthesis-Related Infections/prevention & control , Animals , Biomarkers, Pharmacological/analysis , Dexamethasone/adverse effects , Electrodes, Implanted , Guinea Pigs , Meningitis, Pneumococcal/pathology , Prosthesis Design , Prosthesis-Related Infections/pathology , Scala Tympani/pathology , Scala Vestibuli/pathology
18.
Hear Res ; 289(1-2): 108-15, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22575208

ABSTRACT

In 2002 an increased number of cochlear implant related meningitis cases was reported by the U. S. Food and Drug Administration (FDA). The most commonly identified causative agent was Streptococcus pneumoniae. Although most cases of meningitis were related to a special electrode design, the risk for post-operative pneumococcal meningitis might nonetheless be enhanced by opening of the cochlea during implantation. In the present study, a threshold model for middle ear inoculation of S. pneumoniae was established in the guinea pig after cochlear implantation to assess the post-operative risk of meningitis. Guinea pigs were implanted unilaterally with a silicone cochlear implant electrode dummy. Five weeks after implantation, animals were challenged via the middle ear with a clinically relevant strain of S. pneumoniae and monitored over a period of five days for signs of meningitis. Meningitis was confirmed by clinical outcome in the animals, histological investigation of brains, as well as by pleocytosis and presence of bacteria in cerebrospinal fluid (CSF). By inoculation of varying numbers of bacteria (between 1 × 10(4) and 1 × 10(9) CFU/ml in 10 µl), a threshold model was established. The attack rate, pattern and onset of meningitis depended on number of inoculated bacteria. An increased meningitis rate in different experimental groups shows that greater bacterial burden leads to an increased attack rate after intratympanal inoculation. The established animal model provides a potential tool to assess the meningitis risk after cochlear implantation. Its implementation in future studies will allow the investigation of existing and newly developed prostheses for postoperatively infection risk.


Subject(s)
Cochlea/surgery , Cochlear Implantation/adverse effects , Cochlear Implants/adverse effects , Meningitis, Pneumococcal/microbiology , Prosthesis-Related Infections/microbiology , Streptococcus pneumoniae/pathogenicity , Animals , Cochlea/microbiology , Cochlea/pathology , Cochlear Implantation/instrumentation , Colony Count, Microbial , Disease Models, Animal , Guinea Pigs , Meningitis, Pneumococcal/pathology , Prosthesis-Related Infections/pathology , Risk Assessment , Time Factors
19.
GMS Z Med Ausbild ; 28(4): Doc53, 2011.
Article in English, German | MEDLINE | ID: mdl-22205911

ABSTRACT

The relevance of general medicine at German universities will increase over the next few years. Consequently, the discussion of teaching content and even more the improvement of the structures within the still small and dependent departments of general medicine are of major importance. The example of our department at LMU Munich shows which challenges for leadership and cooperation result from lack of financial and personnel structure. The project "cooperation culture" that the department has conducted in collaboration with the LMU Center for Leadership and People Management is presented as a means to promote leadership and cooperation. This project can serve as an inspiration for the coordinators of smaller departments of general medicine at other German universities that are also striving to improve their structure and their position within the university.


Subject(s)
Cooperative Behavior , Educational Measurement , Faculty, Medical , General Practice/education , Interdisciplinary Communication , Leadership , Attitude of Health Personnel , Data Collection , Female , Germany , Humans , Job Satisfaction , Male , Motivation
20.
Article in English | MEDLINE | ID: mdl-21778784

ABSTRACT

BACKGROUND: Cochlear implant users with residual hearing often benefit greatly from simultaneous electric and acoustic stimulation. However, implantation can cause trauma to the inner ear, resulting in poorer hearing postoperatively. We investigated whether a single local injection of glucocorticoids can reduce hearing loss in long-term implanted guinea pigs. METHODS: Three groups of animals underwent bilateral surgery. One ear was implanted with an electrode, and the contralateral ear received a cochleostomy only. A single dose of the glucocorticoids triamcinolone or dexamethasone, or of artificial perilymph was infused into cochleae via cochleostomy. Compound action potentials were measured before and after application and for 3 months postoperatively. Tissue growth was measured as the percentage of the total area of the scala tympani that was obliterated. RESULTS: Ears subjected to cochleostomy only and treated with glucocorticoids demonstrated a mild hearing loss. In the implanted ears, both glucocorticoids preserved hearing at least temporarily. The volume of tissue growth within the scala tympani was not reduced, and there was no relation between the amount of tissue and hearing loss. CONCLUSIONS: Both glucocorticoids show a potential benefit for hearing preservation in implanted ears. Glucocorticoid therapy may be useful to protect residual hearing during cochlear implantation.


Subject(s)
Cochlea/physiopathology , Cochlear Implants , Evoked Potentials, Auditory/physiology , Glucocorticoids/administration & dosage , Hearing Loss, Sensorineural/surgery , Administration, Topical , Animals , Cochlea/drug effects , Cochlea/surgery , Disease Models, Animal , Ear, Inner/physiopathology , Evoked Potentials, Auditory/drug effects , Guinea Pigs , Hearing Loss, Sensorineural/physiopathology
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